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ForumsMASH / Liver DiseaseMASH resolution without worsening fibrosis — need advice

MASH resolution without worsening fibrosis — need advice

NicoleRaleigh Sun, Dec 28, 2025 at 10:21 AM 11 replies 1,070 viewsPage 1 of 3
NicoleRaleigh
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Dec 28, 2025 at 10:21 AM#1

Writing this once so I can stop repeating it across threads. It is about liver and MASH, and it is deliberately narrow — everything I am not confident about is marked as such.

What is actually established

The liver data is among the strongest non-weight findings in the class. The semaglutide MASH programme reported a large advantage over placebo on MASH resolution, with a substantial minority also achieving fibrosis improvement — and fibrosis is the endpoint that predicts outcomes. Mechanistically it is reduced hepatic lipogenesis, increased fatty-acid oxidation, less hepatic inflammation, and possibly a direct effect on stellate-cell activation.

The condition it depends on

ALT falling is not the same as fibrosis improving. Enzymes are a crude proxy; FIB-4 or elastography is what tells you about the thing that matters.

The practical version

With resmetirom now available for MASH, combination approaches are being explored, so the standard of care in this area is moving faster than most threads assume.

What I am not sure about

What I am trying to establish is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Numbers rather than impressions, if you have them.

— NicoleRaleigh · corrections welcome and will be edited into this post with credit
28 23InsuranceTom, WendyG_ATL, SaraMom3 and 25 others
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labquiet_amy
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Cambridge, MA
Dec 28, 2025 at 11:31 AM#2
NicoleRaleigh said:
The liver data is among the strongest non-weight findings in the class.

ATTAIN trial (survodutide) context for liver and MASH: survodutide, a GLP-1/glucagon dual agonist, showed -18.7% body weight at 46 weeks in the Phase 3 ATTAIN trial. NASH resolution was achieved in ~60% of patients[1].

This is relevant to liver and MASH because survodutide's glucagon agonism specifically targets hepatic lipid metabolism — making it potentially the best-in-class agent for NASH/MAFLD comorbid with obesity.

References:
[1] Sanyal AJ, et al. N Engl J Med. 2024.
27 22HPLC_Greg, LibrarianMeg, bri_stats and 24 others
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Dr.AddMedPHL
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Dec 28, 2025 at 12:41 PM#3
NicoleRaleigh said:
The liver data is among the strongest non-weight findings in the class.

NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy. The Phase 2b data for semaglutide showed 59% NASH resolution (vs 17% placebo) with 43% achieving fibrosis improvement[1].

Mechanism: GLP-1R activation reduces hepatic lipogenesis, increases fatty acid oxidation, reduces hepatic inflammation, and may directly reduce hepatic stellate cell activation (fibrosis pathway).

With resmetirom (thyroid hormone receptor agonist) recently approved for NASH, the field is evolving rapidly. Combination approaches (GLP-1 + resmetirom) are being explored.

References:
[1] Newsome PN, et al. N Engl J Med. 2021;384(12):1113-1124.
Last edited: Dec 28, 2025 at 2:41 PM
26 21mike.trainer_LA, sarah_nash92, FitDadDave and 23 others
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chris_chi24
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Dec 28, 2025 at 1:51 PM#4
Dr.AddMedPHL said:
NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.

Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.

Baseline: "Moderate hepatic steatosis, liver span 17.2cm, echogenic texture consistent with fat infiltration"
Month 8: "Mild steatosis, liver span 15.8cm, improved echogenicity"
Month 14: "Minimal to no steatosis, normal liver span 14.5cm, normal echotexture"

My liver literally shrank and de-fattened. The ultrasound tech said she's seen this pattern increasingly in GLP-1 patients and it's remarkable how consistently the fatty liver resolves.

Last edited: Dec 28, 2025 at 4:51 PM
25 20PurityPaulOR, MaxMetOK, MounjBrad and 22 others
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patPC_UT
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Dec 28, 2025 at 8:32 PM#5
labquiet_amy said:
ATTAIN trial (survodutide) context for liver and MASH: survodutide, a GLP-1/glucagon dual agonist, showed -18.7% body weight at 46 weeks in the Phase…

Mine went the same way, slower.

24 19julia.endo, JessicaM_2024, TomFromTexas and 21 others
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